Objective: To determine whether selective 5lipoxygenase (5-LO) inhibition decreases expression of adhesion molecules (b2 integrins) on systemic neutrophils, decreases neutrophil infiltration in ischemic flap tissue, and improves flap survival. Design: A randomized, controlled study of 91 adult female Hartley guinea pigs divided into 3 survival groups, 4 neutrophil assay groups, 1 sham group, and 1 control group. Ischemia of varying duration and reperfusion was induced in island flank skin flaps. The treated groups received zileuton,a5-LOinhibitor,orallyduringflapischemia.Afterreperfusion, systemic neutrophil receptor expression, neutrophil infiltration, and flap survival were measured. Surface receptormoleculesonneutrophilsfromwholebloodsamples obtained via transcardiac puncture were analyzed using monoclonalantibodiesandcell-associatedfluorescence.Neutrophil infiltration into a distal 1 cm 2 of flap tissue was assessed using myeloperoxidase antibodies. Flap survival was determined within 7 days of surgery. Results: Untreated flaps with 10 hours of ischemia underwent total necrosis. Treated 2- and 10-hour ischemic flaps survived intact. A significant main effect of the drug treatment was detected using analysis of variance (P,.001). Neutrophil receptor detection in the untreated groups undergoing 2 and 10 hours of ischemia was significantly increased compared with that in the treated groups with the same ischemia times. Skin neutrophil infiltration was significantly decreased in the treated groups. Conclusions: Systemic administration of a 5-LO inhibitor is effective in reducing ischemia-reperfusion injury in flap tissue. Our data indicate that there is a significant reduction in neutrophil receptor expression with adminstration of 5-LO, reducing the priming of systemic neutrophils from circulating cytokines.
